EP1218740A2 - Mixing chamber - Google Patents
Mixing chamberInfo
- Publication number
- EP1218740A2 EP1218740A2 EP00958773A EP00958773A EP1218740A2 EP 1218740 A2 EP1218740 A2 EP 1218740A2 EP 00958773 A EP00958773 A EP 00958773A EP 00958773 A EP00958773 A EP 00958773A EP 1218740 A2 EP1218740 A2 EP 1218740A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- reservoir
- mixing
- mixing plate
- plate
- liquid suspension
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
- B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F31/00—Mixers with shaking, oscillating, or vibrating mechanisms
- B01F31/44—Mixers with shaking, oscillating, or vibrating mechanisms with stirrers performing an oscillatory, vibratory or shaking movement
- B01F31/441—Mixers with shaking, oscillating, or vibrating mechanisms with stirrers performing an oscillatory, vibratory or shaking movement performing a rectilinear reciprocating movement
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00279—Features relating to reactor vessels
- B01J2219/00306—Reactor vessels in a multiple arrangement
- B01J2219/00313—Reactor vessels in a multiple arrangement the reactor vessels being formed by arrays of wells in blocks
- B01J2219/00315—Microtiter plates
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00279—Features relating to reactor vessels
- B01J2219/00306—Reactor vessels in a multiple arrangement
- B01J2219/00313—Reactor vessels in a multiple arrangement the reactor vessels being formed by arrays of wells in blocks
- B01J2219/00315—Microtiter plates
- B01J2219/00317—Microwell devices, i.e. having large numbers of wells
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00457—Dispensing or evacuation of the solid phase support
- B01J2219/00459—Beads
- B01J2219/00466—Beads in a slurry
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00479—Means for mixing reactants or products in the reaction vessels
- B01J2219/00481—Means for mixing reactants or products in the reaction vessels by the use of moving stirrers within the reaction vessels
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00497—Features relating to the solid phase supports
- B01J2219/005—Beads
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
- C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N2035/00465—Separating and mixing arrangements
- G01N2035/00534—Mixing by a special element, e.g. stirrer
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1002—Reagent dispensers
Definitions
- the present invention relates to dispensing liquid samples containing particles in liquid suspension.
- the invention relates to a mixing chamber for mixing and maintaining cells, beads, or other particles in liquid suspension and to a method for mixing and maintaining liquid suspensions of cells, beads, or other particles whilst they are being pipetted by means of a robotic workstation.
- scintillant-containing beads are used in automated high throughput screening assays such as radio-immunoassays, receptor binding assays and enzyme assays.
- receptors or other binding agents are immobilised onto the surface of the bead, and are used in the quantitation of analytes, the detection of competitive binding, or in the measurement of enzyme activity.
- cells may be grown in liquid suspension and thereafter treated with active agents such as putative or candidate drug molecules for in-vitro drug metabolism, toxicology and drug profiling studies.
- US Patent No.481 2856 discloses a method and apparatus for dispensing a fluid with dispersed particles using the ink jet principle, the apparatus comprising a reservoir to hold the fluid and dispersed particles and means to agitate the fluid to maintain the dispersed particles in suspension.
- the present invention seeks to provide a mixing chamber which is suitable for mixing particulates in liquid suspension and for dispensing homogeneous samples into microwell plates, which is an alternative to current apparatus and methods and which can be used with a range of particulate sizes and types, both biological and non-biological.
- apparatus for mixing and maintaining particulates in liquid suspension comprising a reservoir for holding a fluid containing dispersed particles, the reservoir having an open top, side walls, end walls and a base; a substantially horizontally-disposed mixing plate mounted inside the reservoir, the mixing plate having a plurality of vertical holes extending through the plate; and means for raising and lowering the mixing plate relative to the reservoir.
- the mixing plate contains an array of holes extending through the plate, the holes being in fixed relationship one with another.
- the mixing plate contains an array of 24-, 96- or 384-holes.
- the reservoir is mounted inside an outer casing which is adapted to include means for engaging with suspension handles of the mixing plate for raising and lowering the mixing plate inside the reservoir.
- means are provided for raising and lowering the mixing plate inside the reservoir, said means comprising at least one piston in contact with the outer casing of the apparatus and operatively connected to an air supply.
- the air supply to the piston (not shown) is controlled by means of a pressure regulator, solenoids and throttle valve so as to deliver bursts or pulses of air to activate the piston.
- the mixing plate may be raised and lowered by means of a toothed drive wheel into which is set an eccentric peg which engages a slot in the outer casing of the apparatus, the drive wheel being driven through a gear train and drive shaft by electric servo drive motor.
- Alternative means for raising and lowering the mixing plate inside the reservoir include a solenoid mechanism, hydraulic pressure activating a piston, or by a magnetic mechanism.
- the apparatus further comprises means for adding samples in liquid suspension to the reservoir by means of a reagent feed pipe and means for removal or re-circulation of unused liquids from the reservoir by means of an overflow pipe.
- the invention provides a method for mixing and maintaining particulate materials in liquid suspension, using the apparatus as described, the method comprising the steps of introducing a liquid suspension of particulate materials to the mixing chamber reservoir, actuating the mixing plate inside the reservoir so as to mix and maintain the particulate materials in liquid suspension.
- the particulate materials may be selected from biological or non-biological sources, for example, cells (eukaryotic cells, prokaryotic cells), viral particles, glass beads, scintillant beads (PVT, polystyrene, yttrium silicate, yttrium oxide), magnetic latex beads, chromatography media, controlled pore glass beads, and the like.
- biological or non-biological sources for example, cells (eukaryotic cells, prokaryotic cells), viral particles, glass beads, scintillant beads (PVT, polystyrene, yttrium silicate, yttrium oxide), magnetic latex beads, chromatography media, controlled pore glass beads, and the like.
- Figure 1 shows a plan view of the apparatus (1 0) according to the invention, including the reservoir (20), the mixing plate (30) and the outer casing (40) components of the apparatus.
- Figure 2 shows a plan view (Figure 2a) and side elevations ( Figures 2b and 2c) of the reservoir (20) according to the invention.
- Figure 3 shows a plan view (Figure 3a) and side elevation (Figure 3b) of the mixing plate (30) according to the invention.
- Figure 4 shows a plan view (Figure 4a) and side elevations ( Figures 4b and 4c) of the outer casing (40) according to the invention.
- Figure 5 is a plot demonstrating maintenance of imaging beads in homogeneous suspension in the mixing chamber according to Example 1 .
- Figure 6 is a plot demonstrating mammalian cell viability following dispensing from the mixing chamber according to Example 2.
- the apparatus ( 1 0) for mixing and maintaining particulates in liquid suspension includes a reservoir (20) (shown in Figure 2) for holding a fluid sample containing dispersed particles.
- the reservoir (20) is rectangular in cross-section, having an open top, side walls (21 a, 21 b), end walls (22a, 22b), and a base (23) .
- the reservoir (20) is sized to accommodate the substantially horizontally-disposed mixing plate (30) such that there is free vertical movement of the mixing plate within the reservoir (20).
- each of the linear guide rail mechanisms being supplied with points for holding the outer casing (40) in registry with the reservoir for guiding the outer casing up and down in relation to the reservoir (20).
- the reservoir includes a horizontally disposed bracket (25) extending from one side wall (21 b).
- a piston (26) is disposed vertically in the horizontally disposed bracket (25) .
- the piston (26) may be positively located to the outer casing by means of a dome-headed locking nut connected to the exposed thread of the piston, in which case retraction of the piston serves to draw the outer casing down over the reservoir in a vertical movement.
- the piston is not positively connected to the outer casing, in which case, the casing is lowered by gravitational force.
- the piston is actuated so as to raise and lower the outer casing (40) and mixing plate (30) components of the apparatus by means of an air supply.
- Control of the air supply to actuate the mixing plate is made possible by well-known means.
- the control of the stroke on the mixing plate is by an electrical timer pulsing a solenoid valve to open at predetermined intervals.
- the air is throttled to alter the severity of the stroke before outputting to the piston.
- the mixing plate is raised and lowered by means of a toothed drive wheel into which is set an eccentric peg which engages a slot in the outer casing of the apparatus.
- the drive wheel is driven through a gear train contained within a detachable housing located on one of the outer side walls (21 a or 21 b) of the reservoir.
- the horizontally disposed bracket (25) and piston (26) are not present.
- the gear train is driven by means of a drive shaft connected to an electric servo drive motor which is located remote from the apparatus.
- the servo drive motor may be contained in an enclosure housing a servo drive unit and programmable logic controller controlled by means of an operator interface, so that the mixing plate of the apparatus may be raised and lowered at a predetermined rate which is related to the level of fluid contained in the reservoir.
- Alternative means for raising and lowering the mixing plate inside the reservoir include hydraulic pressure activating a piston, or by a solenoid or by magnetic means.
- the apparatus has means for adding particulate materials in liquid suspension to the reservoir through a reagent feed pipe (27) set into the lower portion of one end wall (22a) of the reservoir and means for removal or re-circulation of unused liquid samples from the reservoir through a pipe (28) under the control of an outlet valve (not shown).
- reagents or wash solutions may be added to the reservoir by means of a syringe connected to the reagent feed pipe, or by means of a peristaltic pump connected to a second reservoir, or by gravity.
- Reagents may be removed from the reservoir by means of a suction pump connected to the waste pipe.
- the apparatus includes an overflow pipe (29) set into either end wall (22a, 22b) of the reservoir (20).
- the reservoir (20) is of a one-piece moulded construction and may be formed from rigid materials, which are resistant to the aqueous, and/or aqueous/organic media used in the dispensing operation. Suitable materials are selected from stainless steel and rigid plastic or polymeric materials. Alternatively, the reservoir may be formed by machining methods in the surface of a plastic or polymeric block. Preferred plastics are selected from polystyrene, polycarbonate, acetal (polyoxymethylene homopolymer or co-polymer), or poly-tetrafluoroethylene (PTFE; TeflonTM) .
- the mixing plate is shown in Figure 3 and comprises a solid rectangular sheet or block (30) with side walls (31 ), end walls (32), a base (33) and a top (34), wherein there are formed in the block an array of vertical holes (35) extending through the block from the top surface to the base.
- the mixing plate is sized to fit inside the reservoir such that there is free vertical movement of the plate within the reservoir (20) .
- Located in holes (36) drilled into the top surface (34) at each end of the mixing plate are suspension handles (37) secured by a friction fit into the holes.
- the suspension handles are formed from stainless steel and extend upward to connect with lugs located on the outer casing (40) of the apparatus.
- a 384-hole plate (30) is shown having the dimensions 1 2.8 x 8.6 x 0.5cm with the 384 holes in an array of 1 6 rows x 24, spaced apart such that the centre of each hole in the plate is precisely located to coincide with the vertical axis of each of the corresponding wells of a 384-well microplate.
- the mixing plate may be constructed to contain 24-, 96-, or 384-holes as required for dispensing particulate samples into 24- well, 96-well or 384-well microplates.
- Each of the holes in an array is of substantially the same dimensions and is suitably of a diameter which will allow a pipette tip to be inserted through the hole in the mixing plate into the sample contained in the reservoir.
- the diameter of each of the holes in the array may be from 2mm to 7mm, preferably from 2mm to 4mm.
- the diameter of each of the holes in a 384-hole array is preferably 3mm.
- the mixing plate is fabricated from a rigid plastic material, preferably acetal (polyoxymethylene homopolymer or co-polymer), or poly- tetrafluoroethylene (PTFE; TeflonTM) .
- the outer casing (40) of the apparatus is shown in Figure 4 and is sized to fit over the reservoir (20), including the guide rails (24), and piston (26) (or, alternatively, the gear train housing), while allowing free access of a multi-head pipetter to the sample contained in the reservoir.
- the outer casing is formed in rectangular cross-section with side walls (41 a, 41 b), end walls (42a, 42b) and a flange (44) extending horizontally inwards from the vertical walls of the casing.
- lugs (45) suitable for engaging with the suspension handles (37) of the mixing plate (30), for raising the mixing plate.
- the end walls may include one or more slots (46) to allow reagent and waste feed pipe access to the reservoir (20).
- Extending horizontally outwards from the side wall (41 b) is a bracket (47) to which may be connected inside the piston for upward movement of the casing (40).
- the casing is mounted over the reservoir and connected to the guide rails (24) by fixing means, such as screws passing through the outer casing in each end wall.
- the outer casing (40) of the apparatus is of moulded construction and may be formed from rigid materials which are resistant to the aqueous and/or aqueous/organic media used in the dispensing operation.
- the outer casing is fabricated from stainless steel.
- a liquid suspension of particulates is introduced into the reservoir of the assembled apparatus, by means of the reagent feed pipe.
- the air supply is switched on to actuate the piston at predetermined intervals, causing the upward movement of the casing and mixing plate, thereby agitating and mixing the particulates in suspension.
- the outer casing (and mixing plate) are drawn down (or are allowed to return to their original position under gravity) in readiness for the next cycle.
- the mixing plate may be raised and lowered by the toothed drive wheel as described.
- the mixing chamber formed in accordance with the invention By the use of the mixing chamber formed in accordance with the invention and actuating the mixing plate so as to raise and lower the mixing plate, it is possible to mix and maintain particulates in liquid suspension and to remove aliquots of particulate materials in liquid suspension before the materials have had a chance to settle out in the reservoir.
- the invention is further illustrated by reference to the following examples.
- Example 1 An assay to demonstrate maintenance of imaging beads in homogeneous suspension in the mixing chamber
- YOx Streptavidin coated yttrium oxide (YOx) beads (Amersham Pharmacia Biotech) at 20mg/ml were mixed with [ 3 H]biotin at 0.2 ⁇ Ci/mg in the mixing chamber for a period of 5 hours.
- Yttrium oxide beads have a density of
- the mixing chamber was placed on the deck of a MultimekTM 96 (Beckman Coulter) liquid handling device.
- the Multimek was programmed to remove 96 x 10 ⁇ l and add this to one quadrant of a 384 well microplate, this process was repeated a further three times to fill the remaining three quadrants of the 384 well microplate.
- the plate was then imaged on LEADseekerTM Homogeneous Imaging System (Amersham Pharmacia Biotech). Plates were dispensed and imaged every 30 minutes throughout the five-hour mixing period.
- Example 2 An assay to demonstrate mammalian cell viability following dispensing from the mixing chamber
- Method V-79 cells (Chinese hamster lung, ECACC no. 86041 102) were grown in Dulbecco's modified Eagle's minimal essential medium (DMEM), supplemented with 1 0% (w/v) foetal bovine sera (FBS), 2mM L-Glutamine, 50IU/ml Penicillin, 50 ⁇ g/ml Streptomycin to sub-confluence at 37°C in a humidified 5 % CO 2 incubator. The cells were then re-suspended by treatment with Trypsin-EDTA. Cells were diluted to 5000 cells/ml in culture medium.
- DMEM Dulbecco's modified Eagle's minimal essential medium
- FBS foetal bovine sera
- 2mM L-Glutamine 50IU/ml Penicillin
- 50 ⁇ g/ml Streptomycin 50 ⁇ g/ml Streptomycin
- the [ 14 C]thymidine uptake graph displays an increase in mean CPM over time, showing that the V-79 cells were growing and incorporating [ 14 C]thymidine, therefore, indicating that they were still viable following mixing. V-79 cells grew equally well whether mixed manually or using the mixing chamber. After 24 hours of growth the %CV across the 96 well microplate was 2.9 for V-79 cells mixed in the chamber and 4.1 for those mixed manually, indicating that the mixing chamber produced a more homogeneous suspension of cells than achieved manually.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Analytical Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Clinical Laboratory Science (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Pathology (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Sampling And Sample Adjustment (AREA)
- Mixers With Rotating Receptacles And Mixers With Vibration Mechanisms (AREA)
- Engine Equipment That Uses Special Cycles (AREA)
- Automatic Analysis And Handling Materials Therefor (AREA)
- Processing And Handling Of Plastics And Other Materials For Molding In General (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
Description
Claims
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9920924 | 1999-09-06 | ||
GBGB9920924.9A GB9920924D0 (en) | 1999-09-06 | 1999-09-06 | Mixing chamber |
PCT/GB2000/003346 WO2001018539A2 (en) | 1999-09-06 | 2000-09-01 | Mixing chamber |
Publications (2)
Publication Number | Publication Date |
---|---|
EP1218740A2 true EP1218740A2 (en) | 2002-07-03 |
EP1218740B1 EP1218740B1 (en) | 2004-08-11 |
Family
ID=10860356
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP00958773A Expired - Lifetime EP1218740B1 (en) | 1999-09-06 | 2000-09-01 | Mixing chamber |
Country Status (12)
Country | Link |
---|---|
US (1) | US6955462B1 (en) |
EP (1) | EP1218740B1 (en) |
JP (1) | JP2003508224A (en) |
KR (1) | KR20020043574A (en) |
CN (1) | CN1372639A (en) |
AT (1) | ATE273513T1 (en) |
AU (1) | AU7019500A (en) |
BR (1) | BR0013785A (en) |
CA (1) | CA2382147A1 (en) |
DE (1) | DE60012952T2 (en) |
GB (1) | GB9920924D0 (en) |
WO (1) | WO2001018539A2 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014203136A1 (en) * | 2013-06-17 | 2014-12-24 | Reliance Industries Limited | A mixing device and an apparatus employing the mixing device |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6461034B1 (en) * | 2001-11-14 | 2002-10-08 | V & P Scientific, Inc. | Use of a bubble paddle tumble stirrer to mix the contents of a vessel while the contents are being removed |
US20120035596A1 (en) * | 2010-08-04 | 2012-02-09 | Tegg Troy T | Disposable Drive Interface for Longitudinal Movement of an Elongate Medical Device |
US10597623B2 (en) | 2015-11-13 | 2020-03-24 | The Johns Hopkins University | Multiwell cell culture system having rotating shafts for mixing culture media and method of use thereof |
CN106732231A (en) * | 2016-12-21 | 2017-05-31 | 东莞市联洲知识产权运营管理有限公司 | A kind of agitating device in medicine hybrid reactor |
CN108051587B (en) * | 2017-11-03 | 2020-02-14 | 无锡艾科瑞思产品设计与研究有限公司 | ELISA plate with stirring function for food detection |
WO2019126654A1 (en) * | 2017-12-22 | 2019-06-27 | Cuello Joel L | Axial dispersion bioreactor (adbr) for production of microalgae and other microorganisms |
WO2020041762A1 (en) | 2018-08-24 | 2020-02-27 | Cuello Joel L | Mobile and modular cultivation systems for vertical farming |
DE102022208510A1 (en) | 2022-08-17 | 2024-02-22 | Cellcentric Gmbh & Co. Kg | Device for producing a contamination-free dispersion |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US181723A (en) * | 1876-08-29 | Improvement in churns | ||
US401863A (en) * | 1889-04-23 | Milk-can | ||
US292133A (en) * | 1884-01-15 | Assigkoe op one-half to | ||
US190705A (en) * | 1877-05-15 | Improvement in reciprocating churns | ||
US722833A (en) * | 1902-12-15 | 1903-03-17 | James E Furlong | Combined paint-can and paint-mixer. |
US1254429A (en) * | 1916-03-30 | 1918-01-22 | Charles H Parmeley | Automatic painting apparatus. |
US1421571A (en) * | 1919-10-03 | 1922-07-04 | John M Rodger | Power-operated churn |
US2088376A (en) * | 1936-09-05 | 1937-07-27 | Buttermilk Dispensers | Beverage dispenser |
US2681798A (en) * | 1950-04-11 | 1954-06-22 | Muller Hans | Device for mixing, stirring, emulsifying, and pumping, and the acceleration of chemical and physical reactions by vibration |
US2806679A (en) * | 1952-08-05 | 1957-09-17 | Henry H Bruderlin | Ice cream freezer |
US2786040A (en) * | 1953-04-13 | 1957-03-19 | Monsanto Chemicals | Emulsion paints |
US3560162A (en) * | 1968-11-27 | 1971-02-02 | Armour Pharma | Diagnostic device |
US3589685A (en) * | 1969-02-06 | 1971-06-29 | Frederick John Gradishar | Mixing and foam-producing device |
GB8331594D0 (en) * | 1983-11-25 | 1984-01-04 | British Hydromechanics | Non-intrusive agitation of fluid medium |
JPH01217879A (en) * | 1988-02-24 | 1989-08-31 | Tokyo Yamaichi Denki Kk | Terminal metal fittings setting device |
GB9521775D0 (en) | 1995-10-24 | 1996-01-03 | Pa Consulting Services | Microwell plates |
JP2002515044A (en) | 1996-08-21 | 2002-05-21 | スミスクライン・ビーチャム・コーポレイション | A rapid method for sequencing and synthesizing bead-based combinatorial libraries |
-
1999
- 1999-09-06 GB GBGB9920924.9A patent/GB9920924D0/en not_active Ceased
-
2000
- 2000-09-01 BR BR0013785-5A patent/BR0013785A/en not_active Application Discontinuation
- 2000-09-01 WO PCT/GB2000/003346 patent/WO2001018539A2/en active Search and Examination
- 2000-09-01 KR KR1020027002911A patent/KR20020043574A/en not_active Application Discontinuation
- 2000-09-01 JP JP2001522077A patent/JP2003508224A/en active Pending
- 2000-09-01 AT AT00958773T patent/ATE273513T1/en not_active IP Right Cessation
- 2000-09-01 EP EP00958773A patent/EP1218740B1/en not_active Expired - Lifetime
- 2000-09-01 AU AU70195/00A patent/AU7019500A/en not_active Abandoned
- 2000-09-01 US US10/069,694 patent/US6955462B1/en not_active Expired - Fee Related
- 2000-09-01 CN CN00812528A patent/CN1372639A/en active Pending
- 2000-09-01 DE DE60012952T patent/DE60012952T2/en not_active Expired - Fee Related
- 2000-09-01 CA CA002382147A patent/CA2382147A1/en not_active Abandoned
Non-Patent Citations (1)
Title |
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See references of WO0118539A2 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014203136A1 (en) * | 2013-06-17 | 2014-12-24 | Reliance Industries Limited | A mixing device and an apparatus employing the mixing device |
Also Published As
Publication number | Publication date |
---|---|
WO2001018539A2 (en) | 2001-03-15 |
GB9920924D0 (en) | 1999-11-10 |
AU7019500A (en) | 2001-04-10 |
KR20020043574A (en) | 2002-06-10 |
EP1218740B1 (en) | 2004-08-11 |
JP2003508224A (en) | 2003-03-04 |
CA2382147A1 (en) | 2001-03-15 |
WO2001018539A3 (en) | 2001-09-27 |
BR0013785A (en) | 2002-05-14 |
DE60012952T2 (en) | 2005-08-18 |
CN1372639A (en) | 2002-10-02 |
ATE273513T1 (en) | 2004-08-15 |
DE60012952D1 (en) | 2004-09-16 |
US6955462B1 (en) | 2005-10-18 |
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